In the distributed large-scale system, the behavior of any subsystem is not only influenced by variables belonging to it (local variables), but also by the variables in other subsystems during its interaction with neighboring subsystems. The effect of the fault in one subsystem will be quickly propagated to other subsystems due to their interconnections. Currently, most of the fault detection and diagnosis schemes are focused on centralized system which do not consider the interaction terms and can not efficiently detect the faults. In this book, a distributed fault detection scheme is developed for a class of large-scale nonlinear uncertain systems with unstructured modeling uncertainty. For each subsystem in the large-scale system, a fault detection estimator (FDE) is designed by utilizing local measurements and certain communicated information from neighboring FDEs associated with subsystems that are directly interconnected to the particular subsystem under consideration.